Oxyalkyl derivative of the xanthin bases.



"UNITED STATES PATENT OFFICE.

RUDOLPH BERENDES AND FELIX.HER\VIG, OF ELBERFELD; GERMANY, ASSIGNORS TO FARLBENFABRIKEN VORM. FRIEDR. BAYER (St OF ELBERFELD, GERMANY A COR- POBATION OF GERMANY.

OXYALKYL DEIQIVATIVE OF THE XANTHIN BASES.

'. Application filed June 26. 1907- Serial No. 380.783-

To all whom it may concern:

Be it known that we, RUDOLPH BERENDES and FELIX HERWIG, doctors of philosophy,

chemists, citizens of the German Empire, re-

siding at Elberfeld, Kingdoln of Prussia, Germany, have invented new and useful Improvements in New Oxyalkyl Derivatives of the Xanthin Bases, of which the following is a specification.

The xanthin bases, such as Xanthin, theo- 'ph llin, theobromin, methylxanthin, etc.,

s er in respect of their use in medicine from the,disadvantage of being only slightly soluble in 'water and of producing when taken internally toxic symptoms.

We have been successful in preparing the -.hitherto unknown oXyalkyl-derivatives 'of pounds are easily soluble in water.

or their salts, with halogen these bases and have found that these com- They act chemically like alcohols and form esters with acid chlorids, such as acetyl chlorid. By the action of chlor-formic acid ester and subsequent treatment with ammonia urethanes are formed. They are free from any toxic by-effects while the diuretic actionoi' glycol chlorhydrin on' o,H.

glycol bromhydrin, 'lycol iodohydrin, alpha chlorhydrin 011 .0 (311(011) 011 .01, alpha bromhydrin alpha iodohydrin etc. It is advantageous to carry out the reaction in thed presence of agents capable of binding 9.01 s.

In, order to illustrate our invention we give the following example, the parts being by Wei ht: 180 parts of theophyllin' (1.3-dimet 'lxanthin) and 40 parts of NaOH' are disso ved in Water; 80% arts of glycolchlorhydrin are added and t e mixture is then heated to IOU-120 for some hours. The water is removed from the product of the re- Specification of Letters Patent; I

hydrins, such as Patented Dec. 24, 1907.

action by eva oration and the residue is extracted with oiling alcohol which dissolves the 1.3-dimethyl-7-oXy-ethyl-Xanthin. It crystallizes from this solution in the shape of beautiful colorless'leaflets melting at 158 to 160 C. It is easily soluble in water, soluble with more difficulty in alcohol and scarcely soluble in ether and benzene and has the'formula:

H C S\N C=O en CH'OH c =o' b-N 2 N-d-N 011 Its formation probably takes place accordmg to the followlng formula:

orig-N410 o C-NH +010 .011 OH+NaOH= T a OII -1 Il -N //C The 1-oXyethyl-3.7-dimethylxanthin obtainable from glycolchlorhydrin or glycolbromhydrin and theobromin inelts. at 189- 191 C. and forms needles easily soluble in Water.

The 1 di-oxypropyl 3.7-dimethylxanthin obtainable from the bromin and alpha/ 'chlorhydrin has the melting point: 153 to 155 C. and forms colorless needles easily soluble in water.

The 1.7-di-oxyethyl-B-methylXanthin ob tainable from one molecule of S-x'nethylxanthin and two molecules of glycolchlorhydrin forms colorless needles melting at 168 to 170 C. I It is easily solublein water and has the formula:

CHOH.OB2\

\ NC=O C;O (j3 N OH .CH,OH

N -N s/ The process is carried out in an analogous manner if instead of the above mentioned xanthinbases or salts thereof other xanthin' bases containing free ,iminohydro'gens or if instead of the above IHGIIUOIIGd halogen hydrins other halogen hydrins are used.

Having now described our invention and in .what manner the same is to be performed,

i by Letters Patent is op yllin with glycolchlorhydrin, and crys- Correctio n s in Letters Patent No. 874,825.

inlfi like alcohols, forming esters with acid .,and exhibiting valuable therapeutic propwhat we claim as new and desire to secure '1. The herein described new oxyalkyl derivates of xanthin bases obtainable by treating xanthin bases containing replace able hydrogen in'the ilnino groups, with halogen h drins with the addition of agents capable 0 binding acids, and being crystalline compounds easily soluble in water actrids, and by the action of chlor-formic.

acid ester and subsequent treatment withammonia being converted into urethanes;

erties, scribed.

2. The herein described 1 .3-dimethylsubstantially as herelnbefore deoxyethylxanthin obtainable by treating theword be should be stricken outcasein the Patent OfiE'lce.

[snap] Signed and sealedlthis 11th day of February, Ann 1908.-

less ,leaflets melting at 158-160 0., being .easily soluble in water more diflicultly soluing valuable thera eutic pro erties, substantially as hereinbeiore descri ed.

In testimony whereof- We have here .150

set our hands in the presence oftwo lbscribing witnesses.

RUDOLPH BERENDES. FELIX HERWIG.

Witnesses:

O'rro KoNIG, -WILH'ELM FRInnERIcHs;

- It is hereby .certified that in Letters Patent No. 874,825, granted Decernber 24, 1907,

upon the application of Rudolph Berendes and Felix Herwig,

of El berfeld, Germany,

for an improvement in Oxyalkyl Derivatives .of tlie Xanthin Bases, errors appear in the printed specification requiring correction, as follows: In line 28, page 1, the in line 65, same page, on the right side of the t ormula the sign C: H should read (1-11 and in line 82, same page, the words the broniin should read theobroinin; and that the said Letters Patent should 'be read with these corrections therein that the same may conform to the record oi the 0. c. BILLINGS, Acting Commissioner of Patents.,

tallizing from alcohol in the shape of color- 20 i by Letters Patent is op yllin with glycolchlorhydrin, and crys- Correctio n s in Letters Patent No. 874,825.

inlfi like alcohols, forming esters with acid .,and exhibiting valuable therapeutic propwhat we claim as new and desire to secure '1. The herein described new oxyalkyl derivates of xanthin bases obtainable by treating xanthin bases containing replace able hydrogen in'the ilnino groups, with halogen h drins with the addition of agents capable 0 binding acids, and being crystalline compounds easily soluble in water actrids, and by the action of chlor-formic.

acid ester and subsequent treatment withammonia being converted into urethanes;

erties, scribed.

2. The herein described 1 .3-dimethylsubstantially as herelnbefore deoxyethylxanthin obtainable by treating theword be should be stricken outcasein the Patent OfiE'lce.

[snap] Signed and sealedlthis 11th day of February, Ann 1908.-

less ,leaflets melting at 158-160 0., being .easily soluble in water more diflicultly soluing valuable thera eutic pro erties, substantially as hereinbeiore descri ed.

In testimony whereof- We have here .150

set our hands in the presence oftwo lbscribing witnesses.

RUDOLPH BERENDES. FELIX HERWIG.

Witnesses:

O'rro KoNIG, -WILH'ELM FRInnERIcHs;

- It is hereby .certified that in Letters Patent No. 874,825, granted Decernber 24, 1907,

upon the application of Rudolph Berendes and Felix Herwig,

of El berfeld, Germany,

for an improvement in Oxyalkyl Derivatives .of tlie Xanthin Bases, errors appear in the printed specification requiring correction, as follows: In line 28, page 1, the in line 65, same page, on the right side of the t ormula the sign C: H should read (1-11 and in line 82, same page, the words the broniin should read theobroinin; and that the said Letters Patent should 'be read with these corrections therein that the same may conform to the record oi the 0. c. BILLINGS, Acting Commissioner of Patents.,

tallizing from alcohol in the shape of color- 20 It is hereby .certified that in Letters Patent N 0. 874,825, granted December 24, 1907 upon the application of Rudolph Berendes and Felix Herwig, of Elberfeld, Germany, for an improvement in Oxyalkyl Derivatives of the Xanthin Bases, errors appear in the printed specification requiring correction, as follows: In line 28, page 1, the word be should be stricken out; in line 65, same page, on the right side of the forniula. the sign 0 1? should read O --H, and in line 82, same page, the words the bromin should read theobrarnin; and that the said Letters Patent should be read with these corrections therein that the same may conform to the record of the case in the Patent Oflice.

' Signed and sealed this 11th day of February, A. D. 1908.

we o. o. BILLINGS,

Acting Commissioner of Patents. 

